title: The role of the proteasome in the generation of MHC class I ligands and immune responses.
abstract: The ubiquitin-proteasome system (UPS) degrades intracellular proteins into peptide fragments that can be presented by major histocompatibility complex (MHC) class I molecules. While the UPS is functional in all mammalian cells, its subunit composition differs depending on cell type and stimuli received. Thus, cells of the hematopoietic lineage and cells exposed to (pro)inflammatory cytokines express three proteasome immunosubunits, which form the catalytic centers of immunoproteasomes, and the proteasome activator PA28. Cortical thymic epithelial cells express a thymus-specific proteasome subunit that induces the assembly of thymoproteasomes. We here review new developments regarding the role of these different proteasome components in MHC class I antigen processing, T cell repertoire selection and CD8 T cell responses. We further discuss recently discovered functions of proteasomes in peptide splicing, lymphocyte survival and the regulation of cytokine production and inflammatory responses.
authors.affiliation: Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Yalelaan 1, 3584CL Utrecht, The Netherlands, e.j.a.m.sijts@uu.nl
authors.forename: E J A M
authors.initials: EJ
authors.lastname: Sijts
authors.forename: P M
authors.initials: PM
authors.lastname: Kloetzel
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D009124:Muscle Proteins / Q000276:immunology / Q000378:metabolism; D010455:Peptides / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology* / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013950:Thymus Gland / Q000276:immunology / Q000378:metabolism; D014452:Ubiquitins / Q000276:immunology / Q000378:metabolism
chemical_list: D016207:Cytokines; D015395:Histocompatibility Antigens Class I; D008024:Ligands; D009124:Muscle Proteins; C085047:PSME1 protein, human; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014452:Ubiquitins; D046988:Proteasome Endopeptidase Complex